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How Does the ApoE Gene Contribute to Alzheimer’s? Scientists May Have Found the Link

By | September 26th, 2017

Carrying the ApoE4 gene is known as the single largest risk factor for Alzheimer’s, besides age itself. The presence of ApoE4 has been found to increase a person’s risk of developing Alzheimer’s by up to 12 times.

However, it’s never been clear exactly why or how ApoE4 increases the risk of Alzheimer’s when compared to other genetic variants. The presence of beta-amyloid protein plaques in the brain has long been identified as one of the biomarkers of Alzheimer’s, but scientists have not been able to pinpoint ApoE4’s role in its accumulation.

Now, a new study suggests it’s not beta-amyloid that ApoE4 influences to trigger Alzheimer’s; it’s another dementia-associated protein: tau. In the absence of the ApoE gene, tau tangles did little harm to brain cells.

“Once tau accumulates, the brain degenerates,” said study author David Holtzman, MD, the head of the Department of Neurology at Washington University School of Medicine in St. Louis, where the study was conducted. “What we found was that when ApoE is there, it amplifies the toxic function of tau, which means that if we can reduce ApoE levels we may be able to stop the disease process,” said Holtsman in a statement.

Holtzman and his colleagues studied ApoE’s role by observing the brains of mice with the ApoE2, ApoE3 or ApoE4 gene. By nine months of age, mice with any ApoE variant had brain damage. Those with ApoE4 displayed the most damage and ApoE2 the least. Mice without the ApoE gene showed almost none. In humans, those with ApoE4 are more at risk than those with ApoE3, and ApoE2 is considered to be a protective variant against Alzheimer’s disease.

To compare the results in mice to human brains, the researchers at Washington University collaborated with scientists at the University of California, San Francisco. They looked at the autopsies of 79 people who had died from neurodegenerative diseases, and found that those with ApoE4 had more damage in the brain than those without it.

Almost all humans carry one variant of ApoE. Because ApoE is a cholesterol transporter, those rare individuals without it often have very high levels of cholesterol, and usually die from cardiovascular disease at a young age if it’s not treated. Lacking the ApoE variant, however, seems to have no negative effect on the brain.

Since ApoE doesn’t seem to be required for brain function, researchers hope to develop therapies that might target the gene in order to slow down neurodegeneration, even if tau tangles and beta-amyloid are already present.

Read the full write-up here.

One thought on “How Does the ApoE Gene Contribute to Alzheimer’s? Scientists May Have Found the Link

  1. Great article! In terms of practical application, however, we know that abeta precedes tau. ApoE4 carriers are best served trying to avoid/treat the upstream causes of abeta (air pollution, toxins, reduced cerebral glucose metabolism, specific viruses, etc.) before it progresses to the tau stage.

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